Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo.
Hec1 (Highly Expressed in Cancer 1) is one of four proteins of the outer kinetochore Ndc80 complex involved in the dynamic interface between centromeres and spindle microtubules. Its overexpression is seen in a variety of human tumors and correlates with tumor grade and prognosis. We show here that the overexpression of Hec1 in an inducible mouse model results in mitotic checkpoint hyperactivation. As previously observed with overexpression of the Mad2 gene, hyperactivation of the mitotic checkpoint leads to aneuploidy in vitro and is sufficient to generate tumors in vivo that harbor significant levels of aneuploidy. These results underscore the role of chromosomal instability as a result of mitotic checkpoint hyperactivation in the initiation of tumorigenesis.
Diaz-Rodríguez
Elena
E
Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Sotillo
Rocio
R
Schvartzman
Juan-Manuel
JM
Benezra
Robert
R
D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D043171:Chromosomal Instability; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018386:Kinetochores; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins; D008938:Mitosis; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009687:Nuclear Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000494:pharmacology*; D014018:Tissue Distribution
D018797:Cell Cycle Proteins; C533103:Hec1 protein, mouse; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D004318:Doxycycline